lopinavir/r/ lamivudine/ abacavir as an easy to use paediatric formulation

Conditions: HIV

Summary: a phase i/ii, open label, randomized crossover pharmacokinetic, safety and acceptability study of the abacavir/lamivudine/ lopinavir/ritonavir (30/15/ 40/10mg ;4-in-1) fixed-dose combination vs. lopinavir/ritonavir (40/10mg pellets) plus dual abacavir/lamivudine (60/30mg tablets) in hiv infected children. the study is intended to support the adoption of the 4-in-1 by healthcare providers and will provide data that may support its registration in certain countries. the study will be carried out in hiv-infected children in uganda weighing 3 to 25 kg (inclusive) and unable to swallow tablets and will provide supportive clinical data on the pharmacokinetics, safety, tolerability and acceptability of the 4-in-1.

the primary objective is to estimate the population average exposure to lpv, abc and 3tc provided by the 4-in-1 formulation in hiv-infected children dosed per who weight bands. the secondary objectives: * to determine the proportion of children overall, and within each weight band, with a lopinavir c12 \<1.0 mg/l while receiving the 4-in-1 formulation * to evaluate and compare the safety and tolerability of the 4-in-1 formulation versus a reference treatment regimen. * to compare the bioavailability of lpv, abc and 3tc in the 4-in-1 formulation versus a reference treatment regimen. * to assess post exposure cd4 and viral load * to assess the factors that contribute to acceptability of the new 4-in-1 formulation.

Eligibility criteria:
inclusion criteria: * children \> 4 weeks old and weighing ≥3 and \<25 kg at the time of enrolment * past or current documentation of a confirmed diagnosis of hiv infection defined as two positive assays from two different samples. the two results may be in any combination of the following: * at any age: hiv-1 dna pcr positive * documented past hiv-1 rna viral load \> 1,000 copies/ml plasma * at any age \>18 months of age: hiv-1 antibody reactive on two different rapid tests based on national testing algorithm * arv treatment eligible children with lpv-based treatment indication\* as defined by country-specific guidelines or the who paediatric treatment guidelines and confirmed by the investigator * hiv rna viral load \<1000 copies/ml (suppressed) at the screening visit\* * inability to swallow lpv/r tablets * parent or guardian able and willing to provide written informed consent. * for lowest weight band (≥3 and ≤ 5.9kgs) only: under treatment for at least 3 weeks but not more than 12 weeks. * does not apply to the youngest children (≥3 and ≤ 5.9kgs) exclusion criteria: * planned or concurrent use of nnrtis, integrase inhibitors, entry inhibitors, or protease inhibitors (pis) other than lpv/r. * treatment failure with proven resistances to pis. * contraindication to use of pis * clinical condition requiring the use of a prohibited medication (see section 7.6) in association with lpv/r, abc/3tc (refer to section 7.2- 7.3 of the ib) * pulmonary tuberculosis and any clinically significant disease or finding during screening that, in the investigator's opinion, would compromise participation in this study. * treatment with experimental drugs (except for lpv/r pellets) for any indication within 30 days prior to study entry * anticipated transfer of care to a non-participating health facility during the study period